Lomitapide mesylate is a drug for the treatment of hyperchloesterolemia. It has been tested in clinical trials as single treatment and in combinations with atorvastatin, ezetimibe and fenofibrate. The generic name Lomitapide mesylate is marketed by AEGERION under the brand name Juxtapid®.
Lomitapide is chemically, N-(2,2,2-trifluoroethyl)-9-[4-[4-[[[4′-(trifluoromethyl)[1,1′-biphenyl]-2-yl]carbonyl]amino]-1-piperidinyl]-butyl-9H-fluorene-9-carboxamide and has the structural formula:

Lomitapide and its mesylate salt were disclosed in U.S. Pat. No. 5,712,279.
Polymorphism is defined as “the ability of a substance to exist as two or more crystalline phases that have different arrangement and/or conformations of the molecules in the crystal Lattice. Thus, in the strict sense, polymorphs are different crystalline structures of the same pure substance in which the molecules have different arrangements and/or different configurations of the molecules”. Different polymorphs may differ in their physical properties such as melting point, solubility, X-ray diffraction patterns, etc. Although those differences disappear once the compound is dissolved, they can appreciably influence pharmaceutically relevant properties of the solid form, such as handling properties, dissolution rate and stability. Such properties can significantly influence the processing, shelf life, and commercial acceptance of a polymorph. It is therefore important to investigate all solid forms of a drug, including all polymorphic forms, and to determine the stability, dissolution and flow properties of each polymorphic form. Polymorphic forms of a compound can be distinguished in the laboratory by analytical methods such as X-ray diffraction (XRD). Differential Scanning Calorimetry (DSC) and Infrared spectrometry (IR).
Solvent medium and mode of crystallization play very important role in obtaining one polymorphic Form over the other.
Lomitapide and its mesylate salt can exist in different polymorphic Forms, which may differ from each other in terms of stability, physical properties, spectral data and methods of preparation.
We have found two novel polymorphs of Lomitapide. The polymorphs of Lomitapide are stable, reproducible and so, the polymorph of Lomitapide is suitable for pharmaceutical preparations.
The novel polymorphs of Lomitapide are useful intermediate for the preparation of Lomitapide mesylate.
We have also found a novel polymorph of Lomitapide mesylate. The polymorph of Lomitapide mesylate is stable, reproducible and so, the polymorph of Lomitapide mesylate is suitable for pharmaceutical preparations.
Objectives
One objective of the present invention is to provide novel crystalline Forms of Lomitapide, which are stable, reproducible and suitable for pharmaceutical compositions.
Another objective of the present invention is to provide novel amorphous Form of Lomitapide mesylate, which is stable, reproducible and suitable for pharmaceutical compositions.
Another objective of the present invention is to provide the novel amorphous Form of Lomitapide mesylate having high purity greater than 97% by using novel crystalline Forms of Lomitapide of this present invention.